Although modulations in eukaryotic protein synthesis are often attributed to transcriptional changes, it is now clear that post-transcriptional processing, mRNA turnover and mRNA translatability are also important in determining functional mRNA concentrations. Elucidation of the mechanisms which determine mRNA turnover and translatability are therefore important in understanding the regulation of eukaryotic protein synthesis. The metabolic signals which determine the fate of cytoplasm mRNAs are at present unclear, although there is some evidence that both mRNA turnover and translatability may be related to poly (A) metabolism. We have developed techniques to separate mRNAs on the basis of their 3' poly (A) length and to compare the mRNA content of these fractions both by two dimensional gel analysis of their in vitro synthesized peptides and by recombinant DNA technology. Individual mRNAs have very different steady state poly (A) size class distributions, thus suggesting they may indeed have differential rates of both poly (A) processing and degradation. We propose to investigate possible interrelationships between mRNA turnover, poly (A) metabolism and translatability and to establish whether alterations in these parameters modulate the synthesis of specific proteins under different physiological conditions. We shall first determine possible precursor-product relationships between individual polyadenylated and non-adenylated mRNA populations using pulse-labelling and hybridization to recombinant plasmids containing DNAs complementary to actin and the alpha and beta tubulin mRNAs. The stabilities and translational efficiencies of a) different mRNAs with the same average poly (A) length and b) individual mRNAs with different poly (A) lengths will further clarify possible relationships between poly (A) processing, mRNA stability and translation. These parameters will also be compared in differentiated neuroblastoma cells as well as in different phases of the cell cycle.